The American Society for Microbiology (ASM) is responding to the Federal Register announcement of October 17, 2012, Docket CDC-2012-0010: Influenza Viruses Containing the Hemagglutinin from the Goose/Guangdong/1/96 Lineage. The Centers for Disease Control and Prevention (CDC) is seeking feedback on a series of questions regarding this group of viruses. Specifically, CDC is requesting feedback on (1) whether the virus should be added to the Health and Human Services (HHS) list of select agents and toxins and (2) if the virus is added to the HHS select agent list, should it be considered as a Tier 1 select agent.

Given that all highly pathogenic avian influenza viruses are already USDA select agents, the question is whether designating the specific HPAI H5N1 influenza viruses containing the HA gene from the Goose/Guangdong/1/96 lineage an HHS tier 1 agent increases biosafety and biosecurity, i.e. whether it would enhance public health and safety. For the reasons described below, the ASM has concluded that doing so is not warranted at this time.

The virus that contains this hemagglutinin, highly pathogenic avian influenza A (H5N1), or HPAI H5N1, was first identified in 1996 and was first recognized to cause human disease one year later in Hong Kong. Since 2003, HPAI H5N1 has been continuously circulating in wild birds and poultry, with several different clades of the virus having been recognized across wide areas of Asia, Europe, and Africa. The virus has not been identified in the Western Hemisphere, despite speculation that it would cross the Bering Strait and despite intense avian surveillance. In recent years, it has resulted in tens of millions of avian infections and high avian mortality from natural illness and culling efforts.

HPAI H5N1 has also been recognized to cause disease in a number of mammalian species, most important of which are humans. Since late 2003, more than 600 cases of human illness have been recognized, with a mortality rate just under 60 percent. Of note, according to the World Health Organization, no recognized human illness from this virus has been noted anywhere in the world since July 2012, which may be the longest period without human illness in the last decade. And so far, only 30 human cases have been recognized in 2012, the smallest annual number of cases since 2003. This changing human epidemiology may suggest a declining risk or improved prevention and control measures.

In spite of the widespread circulation of HPAI H5N1 over the last 10 years, the number of human illnesses has been very small. This is because human exposure requires close contact with sick and dying poultry coupled with a means of inhaling the virus. Rare examples of human-to-human transmission have been seen, but sustained human transmission has not.

The characteristics and epidemiologic features of human illness do not make naturally circulating strains of HPAI H5N1 that have been seen to date good candidates for inclusion on the select agent list. It is hard to argue that they currently pose a severe threat to human public health and safety, which is the major criterion used to place a pathogen on the HHS select agent list. Although HPAI H5N1 has certain features, including pathogenicity, acute mortality, lack of population immunity and environmental stability, that are consistent with other agents on the select agent list, it has other features that currently make it a poor candidate as a major public health threat. These include communicability, ease of dissemination, and route of exposure. In addition, there is available treatment in the form of antiviral agents and substantial progress has been made in the area of vaccine development.

ASM recognizes that the recent experiments to enhance transmissibility in ferrets are cause for concern, as they demonstrate the ability to genetically manipulate the virus and alter transmission features of naturally occurring HPAI H5N1. However, the impact of such altered viruses in humans is unknown, and it is possible that enhanced transmissibility in humans would result in decreased human morbidity and mortality once the virus becomes better adapted to the upper respiratory tract.

ASM also notes that HPAI H5N1 is already on the list of US Department of Agriculture (USDA) select agents, due to extreme pathogenicity, mortality, and transmissibility in poultry. ASM believes that it is appropriate for this agent to be on the USDA select agent list. As a result of this agricultural designation, HPAI H5N1 already falls under the safety, security, and handling provisions of the select agent rule. Adding HPAI H5N1 viruses to the HHS select agent list will not afford any additional protections or oversight. Thus the practical benefit of adding HPAI H5N1 to the HHS select agent list is unclear, and ASM believes it is unnecessary at this time.

Since the need for HPAI H5N1 to be on the HHS select agent list is questionable, ASM strongly disagrees with the need for this virus to be designated a Tier 1 select agent. As noted above, naturally occurring HPAI H5N1 viruses do not have many of the characteristics of agents that should be included on the Tier 1 list. And such a designation would have serious ramifications for conducting much of the important research necessary to advance our understanding of these viruses and to make further progress on vaccine development. The Tier 1 list should be reserved for agents with a demonstrated ability to cause widespread human public health consequences – and HPAI H5N1 has not demonstrated this feature.

In response to the specific questions raised in the Federal Register:

(1) Do HPAI H5N1 influenza viruses containing the HA gene from the Goose/Guangdong/1/96 lineage pose a severe threat to public health and safety? ASM believes that these viruses are significant concerns due to their high mortality. However, due to the extremely limited number of human illnesses seen despite widespread circulation of the virus and very poor transmissibility, it is hard to argue that the currently circulating viruses represent a severe threat to public health and safety.

(2) Are there other influenza strains containing HA from Goose/Guangdong/1/96 lineage that would also pose a severe threat even if they were not fully of HPAI H5N1 origin? ASM is unaware of such viruses.

(3) Are there any other HPAI H5N1 influenza strains that have been identified to pose a severe threat to public health and safety? ASM is unaware of such viruses.

(4) Should these viruses e regulated as HHS select agents? Since these viruses are on the USDA select agent list and already require the safety and security requirements afforded select agents, ASM believes that there is no added benefit to adding these viruses to the HHS select agent list.

(5) If these viruses should be regulated as HHS select agents, should these viruses be designated as Tier 1 select agents? ASM does not believe these viruses have the characteristics necessary to be designated a Tier 1 agent, and believes such a designation would inhibit important research activities related to these viruses.

(6) Should special precautions (i.e., safety and containment measures) be considered when working with diagnostic specimens suspected of containing HPAI H5N1 influenza viruses containing the HA from the Goose/Guangdong/1/96 lineage (i.e., any precautions versus none at all, precautions beyond those usual for clinical samples and/or laboratory microbes, etc.)? For true diagnostic specimens, clinical and public health laboratories cannot be certain of the specific lineage involved until after specific identification and characterization of the diagnostic specimen. The Select Agent Rule has exempted diagnostic laboratories because of their critical role in early detection of disease outbreaks. Highly pathogenic avian influenza viruses are USDA select agents. If a diagnostic laboratory identifies a select agent, we believe the requirement for diagnostic laboratories to notify CDC and USDA and transfer or destroy the agent in compliance with biosafety and biosecurity regulations is adequate.

(7) Should special precautions (i.e., safety and containment measures) be considered when working with strains of HPAI containing the HA from the Goose/Guangdong/1/96 lineage that have been shown to be transmissible between mammals beyond those recommended for non-mammalian transmissible HPAI (Ref 13 and Ref 14)? Highly pathogenic avian influenza viruses are classified as USDA select agents and must be worked with under BSL-3 with enhancements. We believe BSL-3 practices, procedures and facilities with the addition of respiratory precautions are appropriate for strains that have been genetically manipulated to demonstrate transmissibility between mammals.

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